The overall objective of this NCRR Shared Instrument Grant application is to upgrade and update a heavily-used Institutional Shared DNA Sequencing and Genotyping Core (DNAcore) with an ABI 3730xl DNA Analyzer to 1) lower costs of DNA sequencing and genotyping, 2) increase sequencing read-length and quality, and to 3) provide the new high-throughput ABI SNPlex method for SNP analysis. The requested ABI 3730xl DNA Analyzer is the current state-of-the-art capillary array analyzer that will fulfill all these goals and provide the economy and flexibility needed to satisfy the multitude of user projects requiring our shared resource facility. Of great importance to our investigators working on gene association projects, it will support low to high throughput genotyping utilizing a wide variety of approaches including STR-based linkage, single SNP analyses, allele quantitation by SNaPshot assays, and high throughput genotyping with 48-plex SNPlex assays. This upgrade to our busy shared sequencing, genotyping and oligonucleotide synthesis core facility at Mount Sinai will replace the ageing ABI 3700 platform that is too expensive to run due to its much greater use of reagents, its downtime due to hardware failures, its inability to support the SNPlex assay and its reduced signal sensitivity and uniformity relative to the new ABI 3730xl. This application is strengthened by the previous 10 years of experience of its Principal Investigator in providing high-quality DNA sequencing, genotyping, mutation detection and oligonucleotide synthesis for rapidly increasing numbers of NIH and other investigators at Mount Sinai. The DNAcore provides in-house expertise and consultation services for all sequencing, genotyping, positional cloning, mutation detection, and LOH projects. Equitable, cost-effective and responsive utilization of the requested instrumentation will be promoted through the DNAcore's Local Advisory Committee. They will also identify and recommend novel strategies, technologies, instrumentation, and resources to further facilitate and foster cutting-edge research. The Dean for Research will support service contracts and provide $100K towards the purchase of the requested ABI 3730xl, which with the $65K trade-in for the old ABI 3700 will make this request more cost effective. In addition, the Dean will support technician salaries after another grant terminates next year. With the requested ABI 3730xl DNA Analyzer, the DNAcore will continue to meet intense needs of our over 200 investigators with over 250 NIH grants for economical and accessible on-site sequencing and genotyping services to speed gene discovery, gene structure analysis, mutation characterization, analysis of vector constructs, linkage analysis, genome scanning, LOH studies, etc. In summary, the requested equipment upgrade will fit synergistically with existing resources and our Dean's major genomics initiatives to enhance research productivity by reducing costs of these key services to investigator's grant funds and providing higher quality sequencing and hitherto unavailable analyses to support high-throughput genomic scans. [unreadable] [unreadable] [unreadable]